NATURAL-RESISTANCE OF W/WV MICE TO ETHANOL-INDUCED GASTRIC-LESIONS AND ITS ABROGATION BY BONE-MARROW GRAFTING - POSSIBLE ROLE OF MAST-CELLS AND LTC4

The extent of ethanol-induced acute gastric lesions, gastric leukotriene C4 (LTC4) levels, and the number of gastric mucosal mast cells were examined in mast cell-deficient W/W(v) mice, normal litter-mate +/+ mice, and bone marrow-reconstituted W/W(v) mice. After administration of ethanol, +/+ mice developed gastric lesions and elevation of gastric LTC4 levels in a dose dependent manner. In mast cell-deficient W/W(v) mice, the extent of gastric lesions was far less than that of +/+ mice and the level of gastric LTC4 was not significantly altered. This difference was not due to anemia because blood-transfused non-anemic W/W(v) mice were still resistant to ethanol-induced gastric lesions. When W/W(v) mice were reconstituted with +/+ bone marrow cells, their natural resistance against ethanol-induced gastric lesions was abrogated. The extent of gastric lesions of bone marrow-reconstituted W/W(v) mice paralleled with the increase in number of gastric mucosal mast cells and also with the level of gastric LTC4. Furthermore, ethanol-induced gastric lesions in bone marrow-reconstituted W/W(v) mice was inhibited by pretreatment with 5-lipoxygenase inhibitor, AA-861, in a dose dependent manner. These results suggest that LTC4 may, even if it is not a prerequisite factor for ethanol induced acute gastric lesions, act as the amplitier in the sequential events of the pathogenesis.